Brain injuries which lead to impaired cognitive function remain the least explored area for active neurological intervention. Subjects who suffer severe brain injuries secondary to trauma, hypoxia, infection, and other etiologies typically preserve varying capacities for memory, attention, intention, and awareness. In many cases, these subjects fluctuate dramatically, and even those who regain independence in activities of daily living often fail to reestablish vocational re-entry or other functional levels secondary to persistent cognitive impairment. Such chronic cognitive impairment is typified by failures to recruit sufficient resources of ‘executive functions,’ beginning with vigilance or sustained attentional effort as a primary executive function. Parasuraman, “The Attentive Brain.” Cambridge, Mass.:MIT Press (1998); Sarter et al., “More Attention Must Be Paid: The Neurobiology of Attentional Effort.” Brain Res Rev 51:145-160 (2006). The executive functions further include working memory, motor intention, as well as planning and decision making capacity. Collectively, these executive functions are under joint control of frontal/prefrontal-thalamocortical and frontal/prefrontal-striatopallidal-thalamocortical forebrain systems. The nuclei of the central thalamus (intralaminar and paralaminar regions) play a key role in maintaining levels of activation across these systems and in turn are regulated by ascending projections from the brainstem “arousal systems.” There has been a striking lack of therapeutic options for these patients with broad cognitive impairments resulting from multi-focal structural injuries, despite evidence through their behavioral fluctuations of a latent capacity to further optimize their brain function.
To date, studies in experimental animals demonstrate that electrical stimulation of the central thalamus can improve cognitive function in normal control animals recruiting a reserve capacity present across the forebrain connections of the frontal/prefrontal-thalamic and frontal/prefrontal-striatopallidal-thalamocortical systems in the uninjured brain. Shirvalkar et al., “Cognitive Enhancement With Central Thalamic Electrical Stimulation,” Proc Natl Acad Sci USA., 103(45):17007-12 (2006); Mair et al., “Memory Enhancement With Event-Related Stimulation of the Rostral Intralaminar Thalamic Nuclei,” J Neurosci. 28(52):14293-300 (2008); Shah et al., “Modulation of Arousal Regulation with Central Thalamic Deep Brain Stimulation,” Conf Proc IEEE Eng Med Biol Soc. 3314-7 (2009); Smith et al., “A Bayesian Statistical Analysis of Behavioral Facilitation Associated with Deep Brain Stimulation,” J Neurosci Methods 183(2):267-76 (2009); Schiff, “Central Thalamic Contributions to Arousal Regulation and Neurological Disorders of Consciousness,” Ann N Y Acad Sci. 1129:105-18 (2008). A single-subject human study demonstrated the first proof of the concept that improved arousal regulation produced by stimulation of the central thalamus can facilitate a range of cognitively-mediated behaviors. Schiff et al., “Behavioural Improvements with Thalamic Stimulation After Severe Traumatic Brain Injury,” Nature 448(7153):600-3 (2007). However, improved procedures for controlling and selecting sites within the central thalamus for such stimulation are needed.
The present invention is directed to overcoming these and other deficiencies in the art.